Normothermic Machine Perfusion in Liver Transplantation: Feasibility and Promise of Avoiding Recooling Before Engrafting

2019 ◽  
Vol 25 (7) ◽  
pp. 1113-1117 ◽  
Author(s):  
Fabrizio Francesco ◽  
Duilio Pagano ◽  
Gennaro Martucci ◽  
Davide Cintorino ◽  
Salvatore Gruttadauria
Keyword(s):  
Liver Transplantation ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

Recent advances in liver transplantation

2021 ◽  
pp. flgastro-2020-101425
Author(s):  
N Thomas Burke ◽  
James B Maurice ◽  
David Nasralla ◽  
Jonathan Potts ◽  
Rachel Westbrook
Keyword(s):  
Liver Transplantation ◽  
Survival Rates ◽  
Machine Perfusion ◽  
Allocation System ◽  
Life Saving ◽  
Opt Out ◽  
Normothermic Machine Perfusion ◽  
Marginal Grafts ◽  
Legislative Changes ◽  
The Uk

Liver transplant is a life-saving treatment with 1-year and 5-year survival rates of 90% and 70%, respectively. However, organ demand continues to exceed supply, such that many patients will die waiting for an available organ. This article reviews for the general gastroenterologist the latest developments in the field to reduce waiting list mortality and maximise utilisation of available organs. The main areas covered include legislative changes in organ donation and the new ‘opt-out’ systems being rolled out in the UK, normothermic machine perfusion to optimise marginal grafts, a new national allocation system to maximise benefit from each organ and developments in patient ‘prehabilitation’ before listing. Current areas of research interest, such as immunosuppression withdrawal, are also summarised.

scholarly journals Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

2020 ◽  
Vol 40 (03) ◽  
pp. 264-281 ◽  
Author(s):  
E. Bonaccorsi-Riani ◽  
I.M.A. Brüggenwirth ◽  
J.E. Buchwald ◽  
S. Iesari ◽  
P.N. Martins
Keyword(s):  
Liver Transplantation ◽  
Clinical Trials ◽  
Ex Situ ◽  
Machine Perfusion ◽  
Correct Trial ◽  
Gold Standard Method ◽  
Liver Preservation ◽  
Mature Phase ◽  
Normothermic Machine Perfusion ◽  
Human Livers

AbstractMachine perfusion (MP) preservation is potentially one of the most significant improvements in the field of liver transplantation in the last 20 years, and it has been considered a promising strategy for improved preservation and ex situ evaluation of extended criteria donor (ECD) organs. However, MP preservation adds significant cost and logistical considerations to liver transplantation. MP protocols are mainly classified according to the perfusion temperature with hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) being the two categories most studied so far. After extensive preclinical work, MP entered the clinical setting, and there are now several studies that demonstrated feasibility and safety. However, because of the limited quality of clinical trials, there is no compelling evidence of superiority in preservation quality, and liver MP is still considered experimental in most countries. MP preservation is moving to a more mature phase, where ongoing and future studies will bring new evidence in order to confirm their superiority in terms of clinical outcomes, organ utilization, and cost-effectiveness. Here, we present an overview of all preclinical MP studies using discarded human livers and liver MP clinical trials, and discuss their results. We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation.

scholarly journals Protective role of normothermic machine perfusion during reduced-size liver transplantation in pigs

2016 ◽  
Vol 22 (7) ◽  
pp. 968-978 ◽  
Author(s):  
Zhi-Bin Zhang ◽  
Wei Gao ◽  
Yuan Shi ◽  
Lei Liu ◽  
Ning Ma ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Protective Role ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

2015 ◽  
Vol 22 (1) ◽  
pp. 120-124 ◽  
Author(s):  
Thamara Perera ◽  
Hynek Mergental ◽  
Barney Stephenson ◽  
Garrett R. Roll ◽  
Hentie Cilliers ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Human Liver ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals Machine Perfusion in Liver Transplantation: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-12
Author(s):  
Matas Jakubauskas ◽  
Lina Jakubauskiene ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Transplantation ◽  
Meta Analysis ◽  
Biliary Complication ◽  
Liver Graft ◽  
Machine Perfusion ◽  
Biliary Strictures ◽  
Normothermic Machine Perfusion ◽  
Organ Quality ◽  
End Stage

<b><i>Background:</i></b> Liver transplantation (LTx) is the only treatment option for patients with end-stage liver disease. Novel organ preservation techniques such as hypothermic machine perfusion (HMP) or normothermic machine perfusion (NMP) are under investigation in order to improve organ quality from extended criteria donors and donors after circulatory death. The aim of this study was to systematically review the literature reporting LTx outcomes using NMP or HMP compared to static cold storage (SCS). <b><i>Methods:</i></b> The following data were retrieved: graft primary nonfunction rate, early allograft dysfunction (EAD) rate, biliary complication rate, and 12-month graft and patient survival. A total of 15 studies were included (6 NMP and 9 HMP studies), and meta-analysis was performed only for HMP studies because NMP had considerable differences. <b><i>Results:</i></b> The systematic review showed the potential of NMP to reduce graft injury and lower the liver graft discard rate. The performed quantitative analyses showed that the use of HMP reduces the rate of EAD (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.34–0.76; <i>p</i> = 0.001; <i>I</i><sup>2</sup> = 0%) and non-anastomotic biliary strictures (OR 0.34; 95% CI 0.17–0.67; <i>p</i> = 0.002; <i>I</i><sup>2</sup> = 0%) compared to SCS. <b><i>Conclusion:</i></b> Our systematic review and meta-analysis revealed that the use of HMP reduces the rate of EAD and non-anastomotic biliary strictures compared to SCS.

scholarly journals HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huan Cao ◽  
Longlong Wu ◽  
Xuan Tian ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Rejection ◽  
T Cell Activation ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Inhibitory Receptors ◽  
Donor Liver ◽  
Nkt Cell ◽  
Normothermic Machine Perfusion

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

scholarly journals Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xuan Tian ◽  
Huan Cao ◽  
Longlong Wu ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Transplantation ◽  
Bile Duct ◽  
Progenitor Cells ◽  
Bile Duct Injury ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Marrow Mesenchymal Stem Cells ◽  
Normothermic Machine Perfusion ◽  
Peribiliary Glands

Livers from donors after circulatory death (DCD) are inevitably exposed to a longer warm ischemic period, which might increase the incidence of postoperative bile duct complications. Bone marrow mesenchymal stem cells (BMMSCs) have tissue repair properties. The present study was aimed at exploring the repair effect of heme oxygenase-1- (HO-1-) modified BMMSCs (HO-1/BMMSCs) combined with normothermic machine perfusion (NMP) on bile duct injury after DCD liver transplantation and at revealing the underlying mechanisms. Rat livers were exposed to in situ warm ischemia for 30 min; then, NMP was performed through the portal vein for 4 h with BMMSCs, HO-1/BMMSCs, or neither before implantation. Obvious bile duct histological damage and liver functional damage were observed postoperatively. In the group treated with HO-1/BMMSCs combined with NMP (HBP group), liver functions and bile duct histology were improved; meanwhile, cell apoptosis was reduced and cell proliferation was active. A large number of regenerative cells appeared at the injured site, and the defective bile duct epithelium was restored. Dilatation of peribiliary glands (PBGs), proliferation of PBG cells, high expression of vascular endothelial growth factor (VEGF), and increased proportion of bile duct progenitor cells with stem/progenitor cells biomarkers were observed. Blocking Wnt signaling significantly inhibited the repair effect of HO-1/BMMSCs on bile duct injury. In conclusion, HO-1/BMMSCs combined with NMP were relevant to the activation of biliary progenitor cells in PBGs which repaired bile duct injury in DCD liver transplantation via the Wnt signaling pathway. Proliferation and differentiation of PBG cells were involved in the renewal of the injured biliary epithelium.

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